Skin constitutes the largest organ of the human body, serving as a protective barrier against physical injury, radiation and temperature. The rejuvenation of skin is regulated by various mechanisms including cell-cell interactions, extracellular matrix production and a plethora of polypeptide factor production. One of the major growth factors known to be crucial for skin maintenance, fibroblast growth factor-2 (FGF-2), belongs to a family of similar heparin-binding proteins made by many types of cell, including fibroblasts, melanocytes, endothelial cells. FGF-2 has both a proliferative and motile effect on keratinocytes.
Human skin is made up mainly of two main layers, namely the dermis and the epidermis that superficially covers the dermis. The dermis provides the epidermis with a solid support. It is also its nourishing element. It is made up mainly of fibroblasts and an extracellular matrix composed mainly of collagen, elastin and a substance known as ground substance. These components are synthesized by the fibroblasts.
The skin provides a barrier against external attacks, in particular chemical, mechanical or infectious attacks, and, therefore, a number of defensive reactions against environmental factors (climate, ultraviolet rays, tobacco, etc) and/or xenobiotic, such as, for example, microorganisms, occur therein. This property is referred to as barrier function and is mainly provided by the most superficial layer of the epidermis, namely the horny layer, referred to as the stratum corneum. Detrimental changes in the barrier can be reflected by cutaneous discomfort, sensory phenomena or cutaneous dryness measured by imperceptible water loss.
Skin is the primary barrier between the organism and the outside world. It must both prevent invasion by pathogens but at the same time, prevent water and electrolyte loss from the body. Agents that increase and repair the barrier function of keratinocytes, have great potential as cosmetic skin improving agents. Augmentation of the barrier function increases the skins hydration level and is known to improve the appearance of the skin and lead to a healthier cosmetic appearance.
FGF-2 is detected at the dermis and epidermis near the wound edge (Werner & Grose, Physio Rev 2003). It is also a key regulator in keratinocyte migration during wound healing via its receptor FGF-R1 (Meyer et al, J Cell Sci 2012). FGF-2 binds strongly to heparan sulfate (HS) proteoglycan on the basement membrane of the epidermis and surrounding the hair follicle cross-section (Friedl et al, Am J Pathol 1997).
Cosmetological and dermatological preparations making use of heparan sulfate are known from EP 2 346 573 B1.